Interleukin 2 (IL-2), or T-cell growth factor, is a 15,000 dalton polypeptide in humans which is believed to be responsible for the clonal expansion of norma T lymphocytes during the immune response. Transcription of this small protein is inducible by mitogens such as phytohemagglutinin or concanavalin A in normal human lymphocytes. Recent evidence indicates that it may control the replication of certain human malignant T cells. It has been found that production of IL-2 is completely inhibited by glucocorticoids and cyclosporin A, both of which are powerful immunosuppresive agents. Both glucocorticoids and cyclosporin A inhibit IL-2 production at the level of transcription. The goals of our studies will be to define the factors controlling expression of the IL-2 gene in normal and malignant cells and to attempt to understand the mechanisms through which these factors exert their effects. To this end we have cloned and completely sequenced the human gene for IL-2. We have been making various hybrid gene constructions including linking the Il-2 promoter and 5' sequences to the chloramphenicol acetyl transferase (CAT) structural gene and placing the IL-2 cDNA under the control of the mouse metallothionein or SV40 viral promoters. We have begun to transfect these contructs into various cell types. In collaboration with Yuan DeVries, we have recently found that the IL-2 gene in MLA 144 cells, a gibbon ape T-cell line, is rearranged. The rearrangement is due, at least in part, to the insertion of the gibbon ape leukemia virus (GALV) long terminal repeat (LTR) in the gene. We are attempting to identify the role this viral LTR plays in controlling IL-2 expression in these cells.